One-third of small infants born weighing less than 2,500 grams are not premature but term infants whose growth has been retarded in utero. These infants have a greatly increased incidence of intrapartum asphyxia, neonatal morbidity, neurologic abnormalities and decreased brain cellularity. Intrauterine growth retardation appears to be caused by inadequate flow of nutrients and oxygen from mother to fetus, across the placenta. The metabolic alterations and changes in umbilical uptake of nutrients and oxygen that occur, as growth retardation develops, are unclear. Some types of growth retardation, may be reversible by providing paraplacental nutritional supplements. We propose to evaluate the effects of long-term nutritional therapy on fetuses growth retarded because of maternal malnutrition, fetuses growth retarded because of microinfarction of the placenta, and normal control fetuses. Using a chronic pregnant sheep preparation, with indwelling catheters, we will prospectively follow fetal growth and metabolism, over the six week long third trimester. Some fetuses will be growth retarded by restricting maternal intake of protein and calories and others by embolization of the maternal side of the placenta. One third of the normal fetuses and one third of both groups of growth retarded fetuses will be given continuous intra-amniotic infusions of a nutrient mix (containing amino acids, glucose, lactate and acetate), over the last month of gestation. Another third of each group of fetuses will receive one month of intragastric nutrient infusions. The remaining third will receive no nutritional supplements. In all animals we will follow: fetal weight, fetal length, umbilical uptake of nutrients and metabolite levels in fetal blood, maternal blood and amniotic fluid. The metabolites measured will be: glucose, amino acids, lactate, free fatty acids, beta hydroxybutyrate, acetate, albumin, ammonia, urea, oxygen and blood gases. At birth, fetal carcass content of protein, fat, water and ash will be measured and the DNA and protein content in fetal organs determined.